The invention relates to ion-guide systems for the transfer, cooling, fragmentation, selection and temporary storage of ions.
In mass spectrometers with out-of-vacuum ion generation, it is necessary first to inject the ions into the vacuum system through apertures or capillaries and then to transmit them via various differential pump stages to the actual mass separation system, the mass spectrometric ion analyzer.
Ion transmission has long been achieved using so-called ion guides, which are generally in the form of radio-frequency carrying multi-pole systems such as quadrupole, hexapole or octopole systems consisting of long, thin parallel pole rods. Other systems are also known, e.g. the radio-frequency double helix. By using terminating diaphragms at both ends maintained at an ion-repulsion dc potential, all these systems can also be used as temporary storage devices so that, for example, ions can be injected into a pulsed mass analyzer at the correct times. Pulsed mass spectrometers in this sense include ion-trap mass spectrometers, ion-cyclotron resonance spectrometers and time-of-flight mass spectrometers with orthogonal ion injection.
The ion-guide systems consist of a number of pairs of rods (or pairs of helixes). The two phases of a two-phase radio-frequency voltage supply are applied to two neighboring rods in each case. Barriers of a so-called pseudo-potential are formed between the rods. These barriers hold the ions within the rod system. However, the pseudo-potential barriers are not very high and ions with energies greater than about ten electron volts are able to surmount them.
Radio-frequency ion-guide systems with rod-shaped electrodes have since been adopted for almost all mass spectrometers which operate with out-of-vacuum generated ions such as electrospray ionization (ESI) or atmospheric pressure chemical ionization (APCI). These types of ionization are preferably linked to a device which temporally separates the analyte mixtures by liquid chromatography or capillary electrophoresis. However, ion-guide systems can also be used for ions which have been generated in the vacuum system itself. For example, these types of ion-guide systems are used for ions which are produced by matrix-assisted laser desorption and ionization (MALDI) when they are destined for an ion-trap mass spectrometer (ITMS) or an ion-cyclotron resonance spectrometer (ICRMS or Fourier-transform mass spectrometer FTMS).
In U.S. Pat. No. 5,179,278 (D. J. Douglas), a device and method are described for supplying externally generated ions to an ion trap. In this case, the ions can be temporarily stored and freed of unwanted ions beforehand. The feed system used is an ion-guide system in the form of a multipole, i.e. a quadrupole, hexapole, octopole or higher multipole, with rod-shaped electrodes arranged in parallel to produce a two-dimensional radio-frequency multipole field. According to the claims in the patent, the multipole field is used both for the temporary storage of ions during the time the ions are analyzed in the ion trap and for preselection. Preselection is achieved by resonance ejection of the unwanted ions from the multipole system by the special application of an additional ac voltage to two opposite electrode rods or rod pairs. This method enables unwanted ion species to be removed individually by choosing the frequency of the supplementary ac voltage.
Out-of-vacuum ion generation means that the ions have to be introduced into the vacuum system. Here, a combination of injection capillaries, an initial differential pump stage, a skimmer, a second differential pump stage and a multipole system to capture the divergent, dispersing ions behind the skimmer has proved to be successful, even though by no means all of the ions introduced into the vacuum can be captured with this system. A higher-order multipole system (with a larger number of rods) is the preferred system for capturing a high proportion of the ions emerging from the skimmer at a wide angle. At the very least, a hexapole system or, better still, an octopole system is used for this purpose. With divergent ion bundles, these multipole systems are more efficient for ion capture than quadrupole systems because the reflection at the gridded wall system is better. However, many ions are lost even before the skimmer.
In the first ion-guide system after the skimmer, there is still significant residual pressure of the order of 10xe2x88x921 to 100 Pascals which causes the kinetic energy of ions moving both in the direction of and across the axis to fall very rapidly. The ions tend to collect at the axis of the ion-guide system. With the special addition of a damping gas such as helium to the first or following ion guide systems, the ion beam can also be conditioned by cooling.
In this context, conditioning of the ion beam means decelerating the movement of ions and collecting them in the potential minimum of the pseudo potential at the axis or near the axis of the ion-guide system. With suitable diaphragm systems at the end of the ion guide, the ions can then be drawn from the ion-guide system and formed into a relatively fine, almost parallel ion beam. The conditioning process results in a reduction of the six-dimensional phase space volume which describes the distribution of ions in the position and momentum space. This type of conditioning by reducing the phase space volume, cannot be achieved using ion-optical methods (a consequence of Liouville""s theorem). The phase space volume can only be reduced by so-called cooling processes, e.g. gas cooling or laser cooling. An ion-guide system which conditions the ions by gas cooling for injection into a mass-selecting quadrupole filter was described in U.S. Pat. No. 4,963,736 (D. J. Douglas and J. B. French).
However, the ion-guide systems are not only used for transmitting ions to the mass analyzer. When filled with gas, they can also be used for collisionally induced fragmentation. In this case, ions are injected with higher energies into an ion guide system filled with a collision gas in a certain pressure regime. The fragmentation process is referred to by the abbreviation CID (collisionally induced decomposition). Here too, whether they are fragmented or not, the ions are cooled in the collision gas. The fragmentation process in this ion-guide system (including the frequently used quadrupole system) is the more effective the greater the molecular weight of the collision gas; however, the heavier gases cannot be used since, on collision, the gas molecules frequently deflect the ions sideways so that they are then able to overcome th pseudo-potential barriers between the rods and get lost from the ion guide.
Another arrangement for the time-of-flight mass spectrometers with orthogonal ion injection is disclosed in U.S. Pat. No. 6,011,259 (Whitehouse, Dresch and Andrien) where multipole systems in the form of multipole ion guides are used both for transmitting the ions from out-of-vacuum ion sources to the mass spectrometer and for selecting and fragmenting suitable parent ions. In this case, the gas (usually nitrogen) penetrating into the vacuum system from the external electrospray source at the same time is used as a collision gas for fragmenting the ions and for damping some of the ion movement. Here, the forward movement of the ions must not be damped completely because the multipole rod systems which are used as the ion-guide systems do not provide any active means of forward motion for the ions. The velocity therefore must not be fully damped because otherwise the ions will only be able to leave the ion system by slow diffusion processes. Although these systems can be used to store the ions so that their emptying can be time-controlled according to demand, the ions generated earlier mix with the ions generated later and this interferes with the high temporal resolution of substances separated by rapid chromatography or electrophoresis. On the other hand, ions which have not been decelerated to zero velocity in the gas always have relatively large phase space volumes and are not ideally conditioned for the mass spectrometry which follows.
Similar problems are known for the so-called triple quadrupole mass spectrometers (triple-quad systems) where the central quadrupole system is filled with gas and is used for collisionally induced fragmentation. Also in this case, because of the lack of forward movement, the ions must not be decelerated to zero velocity in the middle stage because otherwise they will only be able to escape by extremely slow diffusion processes.
These radio-frequency multipole ion-guide systems consist of at least two pairs of straight pole rods which are uniformly distributed on the surface of an imaginary cylinder. The rods are supplied with the two phases of a high frequency voltage alternately. If there are two pairs of rods, a quadrupole field is set up inside the rod system; with more than two pairs of rods, a hexapole, octopole, decapole or dodecapole field etc. is produced accordingly. An ion-guide field cannot be produced with just a single pair of straight rods producing a dipolar field, although this is possible with a pair of helical rods. The fields which are produced by pairs of straight rods are frequently (but not very accurately) referred to as two dimensional since this rod arrangement produces the same field distribution at every cross section. In other words, the field distribution only changes in two dimensions and is constant in the third.
The rod systems used to transmit the ions are generally very slender so that the ions are concentrated in an area of very small diameter. They can then be advantageously operated with low radio frequency voltages (a few hundred volts at several MHz frequency) and form a relatively good starting point for further ion-optical imaging of the ions. The cylindrical inner space is often only approximately 3-4 mm in diameter and the rods are usually less than 1 mm thick. The rods are usually fitted into grooves (bonded or soldered), which are located inside the inner aperture of ceramic or plastic rings or are screwed to these rings with spot-welded tabs. The requirement for the inner diameter, i.e. the distances between the rods, to be uniform is relatively strict since non-uniformities in the cross section impede the axial movement of the ions considerably. These systems are therefore not easy to manufacture and are very sensitive to vibration and impacts because they are not very robust. The fragile rod systems are very easily bent out of alignment and cannot be re-adjusted.
If the ion-guide systems are used as ion storage systems in a relatively good vacuum, the ions which are injected into the system at low energy are reflected by the repulsion voltage of the potential diaphragm at the output end and propelled back to the input diaphragm, where they are reflected again at the other end. In this way, they travel back and forth inside the ion-guide system until they are withdrawn by the penetration of a suction field switched on at the output end or until they more or less come to a standstill due to collisions with the residual gas. They are therefore momentarily not available for any kind of use whatever; rather, emptying the ion guide system from ions takes at least as long as it takes for the ions to travel the route twice in the ion-guide system. If the ion-guide system is filled with collision or damping gas in order to damp the movement of ions, removal in a short time becomes even more problematic.
For this reason, for a long time there has been a search for ion-guide systems which allow the ions to be propelled along the axis inside the system. Several methods are presented in U.S. Pat. No. 5,847,386 (B. A. Thomson and C. L. Jolliffe) for which patent claims have been made:
An ion-guide system consisting of a multitude of short rod systems which are axially aligned and where the axis potentials decrease in steps from rod system to rod system;
A rod system consisting of conically tapered rods running parallel to the axis;
A rod system consisting of rods of constant diameters but conically arranged around the axis;
A rod system consisting of rods made from insulating material with an external resistance coating across which a dc voltage drop is produced in additional to the rf voltage;
A rod system with auxiliary electrodes with a weak dc voltage potential between the rods where the auxiliary electrodes are arranged conically in relation to the axis of the system. In each case, the auxiliary electrodes are located at the site of zero potential of the two-phase radio-frequency voltage which alternates between the rods. An axial potential is produced which decreases along the axis.
However, these arrangements are not particularly satisfactory: some are complicated to make, and are therefore not particularly cost effective, while the operation of others is only moderately satisfactory, e.g., the transitions between the separate guide systems result in transmission losses and reflections which can only be partially overcome by using aperture diaphragms connected between. The system with the long auxiliary electrodes between the rods can only be made to operate moderately well in a quadrupole system. Even there, in practice, a large proportion of the ions are lost by touching the auxiliary electrodes which generally reduce the pseudo-potential barriers between the rods. This system is not at all suitable for fragmenting ions since the fragmentation process always scatters the ions in lateral direction so that the losses are far too high. The conical instead of cylindrically shaped ion-guide system almost only moves those ions forward which have not assembled and come to rest in the axis. The same is true for rod systems consisting of tapered rods.
But the propulsion of ions can also be imposed in an ion-guide system by using another method such as transporting the ions by a stream of collision gas. However, it is difficult to produce a sufficiently large flow of gas, which requires high pump performance from the vacuum pumps connected to the system.
Different types of ion-guide systems are disclosed in U.S. Pat. No. 5,572,035 (Franzen) which are quite different from the multipole rod systems described here. One of these consists of only two screw-shaped helical guides in the form of a double helix which are activated by connecting two phases of a radio-frequency voltage. Another system consists of a set of coaxial rings to which the phases of a radio-frequency ac voltage are alternately connected. These systems can also be operated so as to cause the ions to travel along the axis. The double helix can be made from resistance wire which produces a dc voltage drop along its length. The voltage to the individual rings in the ring system can be supplied with a continuously falling dc potential along the path. However, these systems are also not easy and cost-effective to make, since the combination of dc voltages and radio-frequency voltages is always complicated.
But ion-guide systems are not only used for the transmission of ions but also for producing an optimum ion beam as described above. Conditioning ions to form a high quality ion beam is necessary, especially in the case of time-of-flight mass spectrometers with orthogonal ion injection, since the mass resolution of these types of time-of-flight mass spectrometers crucially depends on the spatial and velocity distribution of the ions of the primary beam in the pulser.
Time-of-flight mass spectrometers with orthogonal primary ion-beam injection have a so-called pulser at the start of the flight path which accelerates a section of the primary ion beam, i.e., a thread-shaped ion packet, at right angles to the direction of the beam. This produces a ribbon-shaped secondary ion beam where light ions travel fast and heavy ions travel slowly. The flight direction of the secondary ion beam lies between the direction of the primary ion beam and the direction of acceleration at right angles to it. This type of time-of-flight mass spectrometer is preferably operated with a velocity focussing reflector which reflects the ribbon-shaped secondary ion beam in its entirety and guides it to a detector which is widened to match the beam.
If all the ions fly precisely one behind the other along a single axis and if the ions have no velocity components across the primary beam, then it is easy to see that it is theoretically possible to achieve an infinitely high mass resolution because all the ions of the same mass will be flying precisely on the same front and will reach the detector at precisely the same time. If the primary beam has a finite cross section but none of the ions have a velocity component transverse to the direction of the beam then, due to the spatial focussing behavior of the pulser, it is again theoretically possible to achieve an infinitely high mass resolution (C. Wiley and I. H. McLaren, xe2x80x9cTime-of-flight Mass Spectrometer with Improved Resolutionxe2x80x9d, Rev. Scient. Instr. 26, 1150, 1955). Indeed, a high mass resolution can still be achieved even if there is a strict correlation between the ion location (measured from the axis of the primary beam in the direction of acceleration) and the transverse velocity of the ions in the primary beam in the direction of acceleration. However, if there is no such correlation, i.e., if the ion locations and transverse velocities are distributed statistically without a correlation between the two distributions, then a high mass resolution cannot be achieved.
It is therefore necessary to condition the primary ion beam in relation to its spatial and velocity distribution in order to achieve a high mass resolution in the time-of-flight mass spectrometer.
The six-dimensional space made up of the location and impulse (momentum) coordinates is called the xe2x80x9cphase spacexe2x80x9d. In an ion beam, the location and impulse coordinates of all the ions fill a certain part of the phase space; this part is called the xe2x80x9cphase space volumexe2x80x9d. Conditioning the primary beam therefore always involves a reduction in the phase space volume, at least in the coordinates transverse to the direction of the beam. According to the laws of physics, a reduction in the phase space volume cannot be achieved by ion-optical means but only by cooling the ion plasma of the ion beam, for example, by cooling the plasma by a damping or collision gas. Using a damping gas to cool the ions (at a cost in time) is, for example, the usual method which is used in radio-frequency quadrupole ion traps and provides a satisfactory mass resolution.
Time-of-flight mass spectrometers with orthogonal primary ion-beam injection are used in preference for the scanning of highly resolved mass spectra with fast spectral sequencing in order to track the fast substance separation in rapid separation methods, such as capillary electrophoresis or micro-column chromatography, without time smearing. As well as high mass resolution, it is also desirable for the substance ions introduced one after the other to have a high time resolution. The ions should therefore be cooled in a continuous process in such a way that there is no mixing of earlier and later ions.
Beam conditioning is necessary or at least beneficial for other types of mass spectrometer as well. Every mass spectrometer has a phase-space acceptance cross section which determines which of the injected ions are accepted and which of the injected ions are deflected away or reflected.
The invention consists of embedding elongated ion guides composed of one or more straight, curved or helical rods, which are supplied with single or multiphase radio-frequency voltages, in an external non-zero enveloping dc potential. The dc potential is defined as the potential difference with reference to the mid potential of radio-frequency ac voltage of the rod system. In the following, the inner system, which is made up of rods shaped according to the state of the art, will simply be referred to as the xe2x80x9crod systemxe2x80x9d in contrast to the term xe2x80x9cion-guide systemxe2x80x9d which, in this context, also includes the external envelope electrodes needed to set up the enveloping dc potential. The term xe2x80x9cion-guide systemxe2x80x9d therefore does not refer to the conventional radio-frequency ion-guide systems containing rod systems which are connected to radio-frequencies but which are operated without external enveloping dc voltage and without external enveloping electrodes. The term xe2x80x9celongatedxe2x80x9d will merely refer to the fact that the distance along the rods in the rod system from end to end is longer than the largest diameter of the cross section of their arrangement. xe2x80x9cEmbeddingxe2x80x9d in a dc potential (or xe2x80x9cenvelopingxe2x80x9d with a dc potential) in this context means that the external electrodes are used to create an equipotential surface to surround the rod system even when the enveloping electrodes do not form a closed surface, as in the case of a net or grid.
The combination of a continuously ion-reflecting, radio-frequency pseudo-potential on the rod or rods and an external embedding dc potential results in a new category of ion-guide systems with a series of unexpected properties.
Such a novel ion-guide system is produced, for example, when a rod system, made up of largely parallel rods carrying a single, or multiphase, radio-frequency voltage, is surrounded by an external electrode in the shape of a hollow cylinder connected to an ion-repelling dc voltage. The dc voltage produces an essentially radial electric field between the external electrode on the one hand and the internal rod system on the other. With systems consisting of several rods, the field penetrates through the spaces between the rods or wires and produces a combined field of the penetrating dc voltage field and the continuously repelling pseudo-field of the rods inside the rod system.
The strength of an ac field around a single long wire or rod carrying a radio-frequency decreases outwardly at the rate of 1/r and, within this highly inhomogeneous alternating field, reflects both positively and negatively charged particles above a certain threshold of mass-to-charge ratio. The reason for this is that particles which are sufficiently heavy oscillate in the ac field. The particles, irrespective of their charge, experience the highest acceleration away from the wire exactly when they are at the point in their oscillation nearest to the wire, i.e., at the point of highest field strength, and the highest acceleration toward the wire when it is at the furthest point from the wire, i.e., at the point of lowest field strength. Thus, integrated over time, the particles experience a strong repulsion away from the wire. The repulsion acquired by temporal integration can be described (with reference to the works of Nobel-prize winner Hans Dehmelt) by a xe2x80x9cpseudo dc voltage potentialxe2x80x9d or simply a xe2x80x9cpseudo-potentialxe2x80x9d which is proportional to the square of the ac field strength. Therefore, for a long wire, the repelling pseudo-potential decreases outwards at the rate of 1/r2, where r is the radius. Furthermore, the pseudo-potential is inversely proportional to the mass m of the ion and proportional to the radio-frequency voltage V and the square of the frequency. The threshold for light particles is determined by ability of the lightweight particles either to reach the rod or to escape the reach of the field altogether within a half period of the radio-frequency voltage with the extra energy acquired.
Consequently, each rod independently has a repelling pseudo-potential for sufficiently heavy particles. Between two rods, if the phases of the two ac voltages are different for the different wires, a repelling pseudo-potential with a potential barrier is set up which sags from rod to rod and drops at both sides; it thus forms a saddle. Conventional multipole systems require this saddle-like potential barrier between each pair of neighboring multipole rods in order to keep the ions inside the rod system. However, this is not necessary for the ion-guide systems according to the invention.
In comparison to conventional, multipole ion-guide systems, it is therefore surprising to be able to operate a system consisting of parallel rods even when a single-phase radio-frequency voltage is applied to all the rods equally. This is in sharp contrast to previous radio-frequency, multipole ion-guide systems which require a two or more phase radio-frequency voltage. Consequently, it is also possible to set up an ion-guide system with non-paired rods such as a single straight rod to carry the radio frequency and a tube to carry the ion-repulsion potential.
The simplest system according to the invention therefore consists of a central rod to carry the radio-frequency voltage inside a cylindrical tube that carries the ion-repulsion dc potential with reference to the center radio-frequency voltage on the rod. The pseudo-potential of the rod decreases outwards from the rod at 1/r2 while the dc voltage potential increases outwards with the logarithm ln(r). A cylindrical potential trough is formed from the combined dc voltage and pseudo-potential around the rod where the ions are able to collect. Since the pseudo potential depends on the masses of the ions, the minimum of the potential trough for heavy ions is located nearer the central rod than the minimum for light ions.
If the rod is not located at the axis of the tube but to one side of it nearer to the wall of the tube, then a potential trough is formed around the rod so that the depth of the trough is not symmetrical at all points. The deepest point is in the interior of the tube (see FIG. 2). Looking at the entire length of the tube, the potential minimum will appear as a thread running parallel to the rod inside the tube. Again, the heavier ions will be nearer the rod than the lighter ions. This form of mass separation of the ions can be utilized for a mass spectrometric analysis or ion separation.
From conventional ion-guide systems it is known that the inputs and outputs can be provided with diaphragm systems which prevent the ions from escaping and therefore keep them inside the guide system. This is also true for the ion-guide system according to the invention.
With a knowledge of this invention, it is possible to set up various ion-guide systems with helixes or rod systems consisting of parallel, straight rods carrying one or more phase radio-frequency voltages such as those described below. With a suitable choice of relative dc voltage and radio-frequency voltage strengths, these types of ion-guide systems using rod systems are unique enough to be fundamentally different from conventional multipole, ion-guide systems. It is not necessary to inject the ions into the rod system since it is sufficient to supply them to the ion-guide system anywhere, i.e. even to the space outside the rod system. When the movement energy of ions with a kinetic energy which is not too high is damped in a damping gas, the ions are automatically transferred into the interior of the rod system without any losses since they are never able to reach the envelope electrode or the rods because of the electrical repulsion.
The ion-guide systems according to this invention are particularly suitable for filling with damping gas to cool the ion movements or with collision gas to fragment the ions. The external envelope of potential-carrying electrodes makes it possible to use small quantities of gases and relatively small vacuum pumps.
One of the special features of this novel ion-guide system is that by shaping the external potential, a potential gradient can be set up for the ions which enables them to be guided actively along the length of the ion-guide system through the gas to the output at the end. This can be achieved by setting up an increasing or decreasing potential along the length of the envelope tube, for instance by using a current-carrying resistance coating along the length of the enveloping tube or by using a conical tube for the envelope potential or even by using conical rod systems in cylindrical tubes. Again, using conical rod systems produces unexpected effects which will be explained in more detail below. A coating with resistance material with voltage tappings can be connected in such a way that the direction of acceleration can be reversed or collection pockets can be formed which can be emptied at will by actively forcing the ions to move in the desired direction at the right time.
With this invention, it is possible to construct ion-guide systems which are particularly suitable for conditioning the beam by cooling the ions in a damping gas and for producing a very fine, almost monoenergetic ion beam. These novel ion-guide systems are similarly suitable for fragmenting ions without losses, even for fragmentation by collision with collision gases of high molecular weight such as those which are necessary for certain classes of substances. These systems can also be used to capture ions which are blown into the vacuum of a mass spectrometer with a jet of gas at atmospheric pressure, effectively and without losses.